TY - JOUR
T1 - Folate receptor alpha peptide vaccine generates immunity in breast and ovarian cancer patients
AU - Kalli, Kimberly R.
AU - Block, Matthew S.
AU - Kasi, Pashtoon M.
AU - Erskine, Courtney L.
AU - Hobday, Timothy J.
AU - Dietz, Allan
AU - Padley, Douglas
AU - Gustafson, Michael P.
AU - Shreeder, Barath
AU - Puglisi-Knutson, Danell
AU - Visscher, Dan W.
AU - Mangskau, Toni K.
AU - Wilson, Glynn
AU - Knutson, Keith L.
N1 - Funding Information:
K.R. Kalli is listed as a co-inventor on a patent on immunity to folate receptors, which is owned by the Mayo Clinic and licensed to TapImmune, Inc. M.S. Block reports receiving commercial research support from TapIm-mune, Inc. G. Wilson is an employee of and has ownership interests (including patents) in TapImmune, Inc. K.L. Knutson has ownership interests (including patents) in and is a consultant/advisory board member for TapImmune, Inc. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
This work was supported by grants from the NIH (P50-CA136393-Mayo Clinic SPORE in Ovarian Cancer to Dr. S. Kaufmann and P30-CA015083-Mayo Comprehensive Cancer Center Grant to Dr. R. Diasio), the Fred C. and Katherine B. Andersen Foundation (to K.L. Knutson), the Mayo Clinic Discovery Translation Research Fund (to K.L. Knutson), Department of Defense Breast Cancer Research Program (W81XWH-15-1-0292 to K.L. Knutson), and the Minnesota Ovarian Cancer Alliance (to K.L. Knutson). The authors acknowledge the contributions (conception, design, and acquisition of data) of Dr. Lynn Hartmann, previously of Mayo Clinic (Rochester, MN). The authors also gratefully acknowledge the statistical assistance provided by Dr. Vera Suman, Dr. Amylou Dueck, and Travis Dockter of the Mayo Clinic Comprehensive Cancer Center.
Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Purpose: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity, and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients. Patients and Methods: We conducted a phase I clinical trial testing safety and immunogenicity of this vaccine, enrolling patients with ovarian cancer or breast cancer who completed conventional treatment and who showed no evidence of disease. Patients were initially treated with low-dose cyclophosphamide and then vaccinated 6 times, monthly. Immunity and safety were examined during the vaccine period and up to 1 year later. Results: Vaccination was well tolerated in all patients. Vaccine elicited or augmented immunity in more than 90% of patients examined. Unlike recall immunity to tetanus toxoid (TT), FR T-cell responses developed slowly over the course of vaccination with a median time to maximal immunity in 5 months. Despite slow development of immunity, responsiveness appeared to persist for at least 12 months. Conclusions: The results demonstrate that it is safe to augment immunity to the FR tumor antigen, and the developed vaccine is testable for therapeutic activity in most patients whose tumors express FR, regardless of HLA genotype.
AB - Purpose: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity, and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients. Patients and Methods: We conducted a phase I clinical trial testing safety and immunogenicity of this vaccine, enrolling patients with ovarian cancer or breast cancer who completed conventional treatment and who showed no evidence of disease. Patients were initially treated with low-dose cyclophosphamide and then vaccinated 6 times, monthly. Immunity and safety were examined during the vaccine period and up to 1 year later. Results: Vaccination was well tolerated in all patients. Vaccine elicited or augmented immunity in more than 90% of patients examined. Unlike recall immunity to tetanus toxoid (TT), FR T-cell responses developed slowly over the course of vaccination with a median time to maximal immunity in 5 months. Despite slow development of immunity, responsiveness appeared to persist for at least 12 months. Conclusions: The results demonstrate that it is safe to augment immunity to the FR tumor antigen, and the developed vaccine is testable for therapeutic activity in most patients whose tumors express FR, regardless of HLA genotype.
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U2 - 10.1158/1078-0432.CCR-17-2499
DO - 10.1158/1078-0432.CCR-17-2499
M3 - Article
C2 - 29545464
AN - SCOPUS:85049365468
VL - 24
SP - 3014
EP - 3025
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 13
ER -